title: Angiopoietin-2 Serum Levels Improve Noninvasive Fibrosis Staging in Chronic Hepatitis C: A Fibrogenic-Angiogenic Link.
abstract: Accurate liver fibrosis staging is crucial for the management of chronic hepatitis C (CHC). The invasiveness and cost burden of liver biopsy have driven the search for new noninvasive biomarkers of fibrosis. Based on the link between serum angiopoietin-1 and 2 levels and CHC progression, we aimed to determine the value of these angiogenic factors as noninvasive biomarkers of liver fibrosis.
  
  
  
  Serum levels of angiopoietin-1 and -2 were measured by ELISA in 108 CHC patients who underwent pretreatment liver biopsy. The correlation between angiopoietins and clinical and demographic variables with liver fibrosis was analyzed by univariate regression. Significant factors were then subjected to multivariate analysis, from which we constructed a novel noninvasive liver fibrosis index (AngioScore), whose performance was validated in an independent series of 71 CHC patients. The accuracy of this model was compared with other documented fibrosis algorithms by De Long test.
  
  
  
  Angiopoietins correlated significantly with hepatic fibrosis; however, only angiopoietin-2 was retained in the final model, which also included age, platelets, AST, INR, and GGT. The model was validated and behaved considerably better than other fibrosis indices in discriminating all, significant, moderate and severe liver fibrosis (0.886, 0.920, 0.923). Using clinically relevant cutoffs, we classified CHC patients by discarding significant fibrosis and diagnosing moderate and severe fibrosis with greater accuracy, sensitivity, and specificity.
  
  
  
  Our novel noninvasive liver fibrosis model, based on serum angiopoietin-2 levels, outperforms other indices and should help substantially in managing CHC and monitoring long-term follow-up prognosis.
authors.affiliation: Liver Unit, Gastroenterology Service, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, and CIBERehd, Instituto de Salud Carlos III, Madrid, Spain ; Molecular Biology Unit, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Hernández-Bartolomé
authors.forename: Rosario
authors.initials: R
authors.lastname: López-Rodríguez
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Rodríguez-Muñoz
authors.forename: Samuel
authors.initials: S
authors.lastname: Martín-Vílchez
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Borque
authors.forename: Luisa
authors.initials: L
authors.lastname: García-Buey
authors.forename: Leticia
authors.initials: L
authors.lastname: González-Moreno
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Real
authors.forename: Ricardo
authors.initials: R
authors.lastname: Moreno-Otero
authors.forename: Paloma
authors.initials: P
authors.lastname: Sanz-Cameno
mesh_terms: D000328:Adult; D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood*; D001706:Biopsy; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2